Regulation of connective tissue growth factor gene expression and fibrosis in human heart failure.
Regulation of connective tissue growth factor gene expression and fibrosis in human heart failure.
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DOI：
10.1016/j.cardfail.2013.01.013
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发表时间：
2013-04
影响因子：
6
通讯作者：
Samarel, Allen M.
中科院分区：
文献类型：
--
作者：
Koshman, Yevgeniya E.;Patel, Nilamkumar;Chu, Miensheng;Iyengar, Rekha;Kim, Taehoon;Ersahin, Cagatay;Lewis, William;Heroux, Alain;Samarel, Allen M.
心力衰竭（HF）与细胞外基质（ECM）过度沉积和异常ECM降解相关，导致心脏纤维化。结缔组织生长因子（CTGF）在炎症组织损伤过程中调节ECM的产生，但是关于CTGF基因在衰竭的人类心脏中的表达及其对机械卸载的反应的现有数据有限。对因缺血性（ICM; n=20）和扩张性（DCM; n=20）心肌病接受心脏移植的患者以及非衰竭（NF; n=20）供体心脏的LV组织进行了检查。还分析了接受LV辅助装置（LVAD）植入作为“移植桥”（34-1145天）的患者的配对样本（n=15）。ICM和DCM的间质纤维化程度均高于NF。相对于NF样品，DCM中的羟脯氨酸浓度也显著增加。ICM和DCM中CTGF、TGFB 1、COL 1-A1、COL 3-A1、MMP 2和MMP 9 mRNA的表达与NF对照相比也显著升高。尽管TGFB 1、CTGF、COL 1-A1和COL 3-A1 mRNA水平通过卸载而降低，但组织纤维化仅适度降低，并且LVAD前后组织样品之间的蛋白结合羟脯氨酸浓度没有差异。持续性纤维化可能与卸载后MMP 9 mRNA和蛋白水平的同时降低有关。CTGF可能是适应不良重塑和进展为HF期间纤维化的关键调节因子。虽然机械卸载正常化大多数基因型和功能异常，其对ECM重塑HF期间的影响是不完全的。
Heart failure (HF) is associated with excessive extracellular matrix (ECM) deposition and abnormal ECM degradation leading to cardiac fibrosis. Connective Tissue Growth Factor (CTGF) modulates ECM production during inflammatory tissue injury, but available data on CTGF gene expression in failing human heart and its response to mechanical unloading are limited. LV tissue from patients undergoing cardiac transplantation for ischemic (ICM; n=20) and dilated (DCM; n=20) cardiomyopathies, and from nonfailing (NF; n=20) donor hearts were examined. Paired samples (n=15) from patients undergoing LV assist device (LVAD) implantation as “bridge to transplant” (34-1145 days) were also analyzed. There was more interstitial fibrosis in both ICM and DCM compared to NF hearts. Hydroxyproline concentration was also significantly increased in DCM relative to NF samples. The expression of CTGF,TGFB1, COL1-A1, COL3-A1, MMP2 and MMP9 mRNAs in ICM and DCM were also significantly elevated as compared to NF controls. Although TGFB1, CTGF, COL1-A1, and COL3-A1 mRNA levels were reduced by unloading, there was only a modest reduction in tissue fibrosis and no difference in protein-bound hydroxyproline concentration between pre- and post-LVAD tissue samples. The persistent fibrosis may be related to a concomitant reduction in MMP9 mRNA and protein levels following unloading. CTGF may be a key regulator of fibrosis during maladaptive remodeling and progression to HF. Although mechanical unloading normalizes most genotypic and functional abnormalities, its effect on ECM remodeling during HF is incomplete.
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DOI：
10.1161/atvbaha.111.235549
发表时间：
2011-11
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
--
作者：
Koshman YE;Chu M;Engman SJ;Kim T;Iyengar R;Robia SL;Samarel AM
通讯作者：
Samarel AM
影响因子：
6.5
作者：
Frazier, K;Williams, S;Grotendorst, GR
通讯作者：
Grotendorst, GR
影响因子：
4.8
作者：
Hishikawa, K;Oemar, BS;Fujii, T
通讯作者：
Fujii, T
影响因子：
15.9
作者：
ELEFTHERIADES, EG;DURAND, JB;SAMAREL, AM
通讯作者：
SAMAREL, AM
影响因子：
8.9
作者：
Felkin, Leanne E.;Lara-Pezzi, Enrique;Barton, Paul J. R.
通讯作者：
Barton, Paul J. R.